The overall goal of this project is to improve image-guided intra-operative mapping of eloquent regions by improved characterization of eloquent pathways within and surrounding brain lesions. We propose to develop, validate, and optimize a technique that we hypothesize will improve the efficacy and reduce the functional deficits of image-guided resection of brain tumors. Furthermore, we expect that these methods will warrant subsequent multi-center clinical investigations with the ultimate goal of providing information that allows for more aggressive interventions while preserving eloquent areas. Diffusion tensor MRI (DTI) has emerged as a potential technique to aid in pre-operative planning and intra- operative mapping of eloquent pathways. While we have had some success in identifying eloquent regions, uncertainties in the DTI estimated fiber directions due to tumor, edema, and complex white matter have limited our success. Additionally, DTI -fiber tracking cannot distinguish fiber tracts that may be non- functioning due to damage by the lesion. Our previous studies have indicated false negative identification of pathways passing through and within the margins of lesions that were detected by intra-operative electrical stimulation (IES). The recent development of high-angular resolution diffusion MRI (HARDI) provides fiber direction information within edematous regions and at fiber crossings, and may improve pre-operative identification of eloquent pathways in brain tumor patients. At UCSF, we have a group of collaborators that is uniquely suited to develop a method for identifying eloquent areas during surgical intervention by combining pre-operative imaging and intra-operative white matter mapping. The pre-operative imaging includes HARDI to detect the axonal structures, MR spectroscopic imaging to determine functioning axons via the NAA concentration, and T2 spectroscopy to identify myelin fraction. The ability of these complementary imaging methods to detect the presence of functioning pathways will be validated by image-guided electrical stimulation at the margins of tumors. If successful, this comprehensive framework will greatly improve pre-operative characterization of axonal pathways in and around tumors and aid in image-guided intra-operative mapping of eloquent regions and pre-operative characterization of functional pathways that benefit surgical and radiation therapy strategies. [unreadable] [unreadable] [unreadable]